Low-renin hypertension (LRH), in a small subset of patients is probably caused by an increased secretion of a mineralocorticoid. To date the separation of these patients from the much larger set of LRH patients without a mineralocorticoid etiology has been very difficult. We are proposing to use a plasma mineralocorticoid radioreceptor assay using a pituitary tumor cell line, GH3D6, as the source of the binding protein, to identify patients with a mineralocorticoid syndrome. Whole cells are incubated with plasma from patients equilibrated with (1, 2, 6, 7 3H) aldosterone and the specific cell bound radioactivity is measured and compared to a dose response curve of unlabelled aldosterone in charcoal extracted plasma. To determine if unexplained activity exists, the patients plasma is stripped of all steroids with charcoal, then known steroids are added at concentrations to match those previously measured in the same plasma and their competitive activity is determined. In this way patients with unexplained mineralocorticoid activity can be identified. A second project involves the study of the biological activity and measurements in urine and plasma of 18-hydroxycortisol. This steroid was recently isolated in patients with aldosterone producing adrenal adenomas by S. Ulick's group. The biological activity will be measured using standard glucocorticoid, and mineralocorticoid bioassays, its hypertensinogenic activity will also be determined by chronic injection into rats. A radioimmunoassay will be developed for 18-hydroxycortisol and the urine and plasma of patients with primary aldosteronism, low renin hypertension and normal renin hypertension will be thus assayed to determine the prevalence of the abnormality and to find out whether this measurement can serve to differentiate patients with aldosterone producing adenomas vs. hyperplasia.